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CONCISE REVIEW |
a Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’ Immacolata, Rome, Italy;
b Center for Animal Transgenesis and Germ Cell Research, Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA
Key Words. Oct-4 expression levels • Embryonic stem cell totipotency • Differentiation • Oct dimer configurations
Correspondence:
Hans R. Schöler, Ph.D., Director, Center for Animal Transgenesis and Germ Cell Research, Germline Development Group, New Bolton Center, 382 W. Street Rd., Kennett Square, Pennsylvania 19348, USA. Telephone: 610-444-5800 x2289; Fax: 610-925-8121; e-mail: scholer{at}vet.upenn.edu
The Oct-4 POU transcription factor is expressed in mouse totipotent embryonic stem and germ cells. Differentiation of totipotent cells to somatic lineages occurs at the blastocyst stage and during gastrulation, simultaneously with Oct-4 downregulation. Stem cell lines derived from the inner cell mass and the epiblast of the mouse embryo express Oct-4 only if undifferentiated. When embryonic stem cells are triggered to differentiate, Oct-4 is downregulated thus providing a model for the early events linked to somatic differentiation in the developing embryo. In vivo mutagenesis has shown that loss of Oct-4 at the blastocyst stage causes the cells of the inner cell mass to differentiate into trophectoderm cells. Recent experiments indicate that an Oct-4 expression level of roughly 50%-150% of the endogenous amount in embryonic stem cells is permissive for self-renewal and maintenance of totipotency. However, upregulation above these levels causes stem cells to express genes involved in the lineage differentiation of primitive endoderm. These novel advances along with latest findings on Oct-4-associated factors, target genes, and dimerization ability, provide new insights into the understanding of the early steps regulating mammalian embryogenesis.
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A. Bortvin, K. Eggan, H. Skaletsky, H. Akutsu, D. L. Berry, R. Yanagimachi, D. C. Page, and R. Jaenisch Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei Development, April 15, 2003; 130(8): 1673 - 1680. [Abstract] [Full Text] [PDF]
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B. Li, F.-C. Yang, D. W. Clapp, and K. T. Chun Enforced expression of CUL-4A interferes with granulocytic differentiation and exit from the cell cycle Blood, March 1, 2003; 101(5): 1769 - 1776. [Abstract] [Full Text] [PDF]
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M. Buehr, J. Nichols, F. Stenhouse, P. Mountford, C.J. Greenhalgh, S. Kantachuvesiri, G. Brooker, J. Mullins, and A.G. Smith Rapid Loss of Oct-4 and Pluripotency in Cultured Rodent Blastocysts and Derivative Cell Lines Biol Reprod, January 1, 2003; 68(1): 222 - 229. [Abstract] [Full Text] [PDF]
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M. Jackson, J. W. Baird, N. Cambray, J. D. Ansell, L. M. Forrester, and G. J. Graham Cloning and Characterization of Ehox, a Novel Homeobox Gene Essential for Embryonic Stem Cell Differentiation J. Biol. Chem., October 4, 2002; 277(41): 38683 - 38692. [Abstract] [Full Text] [PDF]
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R. G. Hawley and D. A. Sobieski Stem Cell Bouillabaisse-Potpourri Stem Cells, September 1, 2002; 20(5): 360 - 363. [Full Text] [PDF]
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 D. Solter Cloning v. clowning Genes & Dev., May 15, 2002; 16(10): 1163 - 1166. [Full Text] [PDF]
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M. Boiani, S. Eckardt, H. R. Scholer, and K. J. McLaughlin Oct4 distribution and level in mouse clones: consequences for pluripotency Genes & Dev., May 15, 2002; 16(10): 1209 - 1219. [Abstract] [Full Text] [PDF]
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Y. Guo, R. Costa, H. Ramsey, T. Starnes, G. Vance, K. Robertson, M. Kelley, R. Reinbold, H. Scholer, and R. Hromas The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression PNAS, March 19, 2002; 99(6): 3663 - 3667. [Abstract] [Full Text] [PDF]
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